Synthesis, characterization, and biological activity of oxovanadium(IV) complexes with polyalcohols

Oxovanadium(IV) complexes of the polyalcohols sorbitol, galactitol, and mannitol, of stoichiometry Na(2)[VO(L)(2)].H(2)O, were obtained from aqueous alkaline solutions. They were characterized by elemental analysis, infrared and UV-vis spectroscopies, thermoanalytical (thermogravimetric and differential thermal analysis) data, and magnetic susceptibility measurements. The biological activities of the complexes on the proliferation, differentiation, and glucose consumption were tested on osteoblast-like cells (MC3T3E1 osteoblastic mouse calvaria-derived cells and UMR106 rat osteosarcoma-derived cells) in culture. The three complexes exerted a biphasic effect on cell proliferation, being slight stimulating agents at low concentrations and inhibitory in the range of 25-100 microM. All the complexes inhibited cell differentiation in tumor osteoblasts. Their effects on glucose consumption were also discussed. The free ligands did not show any effect on the studied biological parameters.     

Vanadyl tetradentate Schiff base complexes as catalyst for C-H bond activation of olefins with tert-butylhydroperoxide: Synthesis, characterization and structure

Three N₂O₂ tetradentate Schiff base ligands (H₂L^1-3) were prepared by reaction of 1,2-propylenediamine and appropriate aldehyde and ketone and characterized by FT-IR, ¹H and ¹³C NMR. The vanadyl complexes were synthesized by treating an ethanolic solution of the appropriate ligand and one equivalent of VO(acac)₂ to yield VOL^1-3. These oxovanadium (IV) complexes were characterized on the basis of their FT-IR, UV-Vis spectroscopy and elemental analysis. The crystal structure of VOL³ has been determined. The metal center in VOL³ is a deformed tetragonal pyramidal N₂O₃ coordination sphere. These complexes are used as catalyst for the selective epoxidation of olefins. High selectivity of epoxidation for cyclooctene observed from oxidation data. The catalytic activity increases as the number of electron-donor groups increases, and the catalytic selectivity is varied by changing the substituents on the ligands. The catalytic system described here is an efficient and inexpensive method for the oxidation of olefins, with the advantages of high activity, selectivity, re-usability and short reaction time.     

Enhancement of insulin signaling pathway in adipocytes by oxovanadium(IV) complexes

Recently, we have found that some oxovanadium(IV) complexes are potent insulin-mimetic compounds for treating both type I and type II diabetic animals. However, the functional mechanism of oxovanadium(IV) complexes is not fully understood. In this report, we have shown that oxovanadium(IV)-picolinate complexes such as VO(pa)(2), VO(3mpa)(2), and VO(6mpa)(2) act on the insulin signaling pathway in 3T3-L1 adipocytes. Among them, VO(3mpa)(2) was found to be the highest potent activator in inducing not only the phosphotyrosine levels of both IRbeta and IRS but also the activation of downstream kinases in the insulin receptor, such as Akt and GSK3beta, which in turn translocated the insulin-dependent GLUT4 to the plasma membrane. Then, we examined whether or not oxovanadium(IV)-picolinates exhibit the hypoglycemic activity in STZ-induced diabetic mice, and found that VO(3mpa)(2) is more effective than the others in improving the hyperglycemia of the animals. Our present data indicate that both activation of insulin signaling pathway, which follows the GLUT4 translocation to the plasma membrane, and enhancement of glucose utilization by oxovanadium(IV) complexes cause the hypoglycemic effect in diabetic animals.     

The solution structure of bis(acetylacetonato)oxovanadium(IV)

The behaviour of the bis-chelated oxovanadium(IV) complexes formed by acetylacetone (acac) and five of its derivatives was re-examined through a combination of spectroscopic methods in different solvents. It has been found that the complexes are penta-coordinated with a geometry close to the square pyramid and maintain in solution the same structure as in the solid state. The results rule out a cis-trans isomerism of the species VOL₂S (L = acac or derivative, S = solvent) in solution. Depending on the coordinating ability of the solvent a sixth molecule can be bound, more or less strongly, to the free axial position of the complexes. The combined application of the electronic absorption and IR spectroscopies allows to establish if the complexes in solution are penta- or hexa-coordinated.     

Synthesis, characterization, and protein tyrosine phosphatases inhibition activities of oxovanadium(IV) complexes with Schiff base and polypyridyl derivatives

Seven new mixed-ligand vanadyl complexes, [V^IVO(5-Br-SAA)(NN)] and [V^IVO(2-OH-NAA)(NN)] (1-7) (5-Br-SAA for 5-bromosalicylidene anthranilic acid, 2-OH-NAA for 2-hydroxy-1-naphthaldehyde anthranilic acid and NN for N,N′-donor heterocyclic base, namely, 2,2′-bipyridine (bpy, 1 and 5), 1,10-phenanthroline (phen, 2 and 6), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, 3 and 7), dipyrido[3,2-a:2′,3′-c]phenazine (dppz, 4)), were synthesized and characterized. X-ray crystal structure of [V^IVO(5-Br-SAA)(phen)] revealed a distorted octahedral geometry with the Schiff base ligand coordinated in a tridentate ONO-fashion and the phenanthroline ligand in a bidentate fashion. Density-functional theory (DFT) calculations suggest a similar structure and the same coordination mode for all the other oxovanadium complexes synthesized. Biochemical assays demonstrate that the mixed-ligand oxovanadium(IV) complexes are potent inhibitors of protein tyrosine phosphatase 1B (PTP1B), with IC₅₀ values approximately 41-75 nM. Kinetics assays suggest that the complexes inhibit PTP1B in a competitive manner. Notably, they had moderate selectivity of PTP1B over T-cell protein tyrosine phosphatase (TCPTP) (about 2-fold) and good selectivity over Src homology phosphatase 1 (SHP-1) (about 4∼7-fold). Thus, these mixed-ligand complexes represent a promising class of PTP1B inhibitors for future development as anti-diabetic agents.     

Bactericidal activity of different oxovanadium(IV) complexes with Schiff bases and application of chelation theory

Oxovanadium(IV) complexes have been synthesized and characterized the general composition [VOL(A)], where H₂L = salicylidene-o-aminothiophenol A¹ = bis(benzylidene)ethylenediamine, A² = bis(acetophenone)ethylenediamine, A³ = 2,2′-bipyridylamine, A⁴ = bis(benzylidene) ? 1,8-diaminonaphthalene, A⁵ = thiophene-o-carboxaldeneaniline and A⁶ = thiophene-o-carboxaldene-p-anisidine. Spectral studies indicate that the oxovanadium(IV) complexes assume a six-coordinate octahedral geometry. The antibacterial activities of the complexes against Salmonella typhi, Escherichia coli and Serratia mercescens are higher as compared to the free ligands, vanadyl sulphate, and the control (DMSO) but of moderate activity as compared to the standard drug (tetracycline).     

Ternary oxovanadium(IV) complexes of ONO-donor Schiff base and polypyridyl derivatives as protein tyrosine phosphatase inhibitors: synthesis, characterization, and biological activities

Abstract  A series of oxovanadium complexes with mixed ligands, a tridentate ONO-donor Schiff base ligand [viz., salicylidene anthranilic acid (SAA)], and a bidentate NN ligand [viz., 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq), dipyrido[3,2-a:2′,3′-c]phenazine (dppz), or 7-methyldipyrido[3,2-a:2′,3′-c]phenazine (dppm)], have been synthesized and characterized by elemental analysis, electrospray ionization mass spectrometry, UV–vis spectroscopy, Fourier transform IR spectroscopy, EPR spectroscopy, and X-ray crystallography. Crystal structures of both complexes, [V^IVO(SAA)(bpy)]·0.25bpy and [V^IVO(SAA)(phen)]·0.33H₂O, reveal that oxovanadium(IV) is coordinated with one nitrogen and two oxygen atoms from the Schiff base and two nitrogen atoms from the bidentate planar ligands, in a distorted octahedral geometry (VO₃N₃). The oxidation state of V(IV) with d ¹ configuration was confirmed by EPR spectroscopy. The speciation of VO–SAA–bpy in aqueous solution was investigated by potentiomtreic pH titrations, and the results revealed that the main species are two ternary complexes at a pH range of 7.0–7.4, and one is the isolated crystalline complex. The complexes have been found to be potent inhibitors against human protein tyrosine phosphatase 1B (PTP1B) (IC₅₀ approximately 30–61 nM), T-cell protein tyrosine phosphatase (TCPTP), and Src homology phosphatase 1 (SHP-1) in vitro. Interestingly, the [V^IVO(SAA)(bpy)] complex selectively inhibits PTP1B over the other two phosphatases (approximate ninefold selectivity against SHP-1 and about twofold selectivity against TCPTP). Kinetics assays suggest that the complexes inhibit PTP1B in a competitive and reversible manner. These suggest that the complexes may be promising candidates as novel antidiabetic agents. Graphical Abstract   Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis and characterization of some oxovanadium(V) complexes with internally functionalized oximes: Crystal and molecular structures of heptacoordinated [VO{ONC(CH3)(C4H3O-2)}3] and [VO{ONC(CH3)(C4H3S-2)}3] · 0.5C6H6

New oxovanadium(V) complexes with internally functionalized oximes of the type VO{OPrⁱ}_3−n{ONC(CH₃)(Ar)}_n] (where Ar = C₄H₃O-2, C₄H₃S-2 and C₅H₄N-2 and n = 1-3) have been prepared in quantitative yields by the reaction of VO(OPrⁱ)₃ with the corresponding oximes in various stoichiometric ratios in refluxing anhydrous benzene. The products have been characterized by elemental analyses and spectroscopic (FT IR, ¹H, ¹³C{¹H} and ⁵¹V NMR) studies. FAB mass spectral analysis of [VO{OPrⁱ}{ONC(CH₃)C₄H₃S}₂] indicates the monomeric nature of the complex. ⁵¹V NMR values for these complexes suggest the formation of tetra-coordinate species in solution. However, the single crystal X-ray diffraction studies of [VO{ONC(CH₃)(C₄H₃O-2)}₃] and [VO{ONC(CH₃)(C₄H₃S-2)}₃] · 0.5C₆H₆ exhibit the presence of vanadium(V) atoms in a unique hepta-coordination state with distorted pentagonal bipyramidal geometry in the solid state. The oxo- atom occupies the axial position while the oximato ligands are bonded in a dihapto (η²-N,O) manner with the formation of three membered rings.     

Synthesis, characterisation and insulin-mimetic activity of oxovanadium(IV) complexes with amidrazone derivatives

The complexation of VO(2+) ion by ten acetamidrazone and 2-phenylacetamidrazone derivatives (L) was studied. Sixteen novel VO(2+) complexes were synthesised and characterised through the combined application of analytical and spectroscopic (EPR (electron paramagnetic resonance), FT-IR and diffuse reflectance electronic absorption) techniques. Eight are 1:2 species of composition [VOL(2)]SO(4) x xH(2)O and eight are 1:1 species with formula [VOL(SO(4))](n) x xH(2)O. The experimental data suggest a bidentate coordination mode for L with the donor set formed by the imine nitrogen and the carbonyl oxygen. EPR spectra indicate a square-pyramidal geometry for the 1:1 complexes and a penta-coordinated geometry intermediate between the square-pyramid and the trigonal-bipyramid for the 1:2 species. The hyperfine coupling constant along z axis, A(z), of the 1:2 complexes exhibits a marked reduction with respect to the predicted value (approximately 148x10(-4)cm(-1) vs. approximately 170x10(-4)cm(-1)). IR spectroscopic evidence supports the presence of sulphate as a counter-ion in the 1:2, and as a bridging bidentate ligand in the 1:1 complexes. Insulin-mimetic tests on modified fibroblasts, based on a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide) assay, performed on three of the bis-chelated and eight of the mono-chelated derivatives, indicate that they are biologically active. The similar hydro/lipophilicity and the lack of ligand substituents recognizable by cell membrane receptors prevent substantial differentiation in the insulin-mimetic action.